DESCRIPTION: The ability of photothermal biomaterials to convert light to heat can have diverse applications in medicine. However, the lack of effective biomaterials has adversely impacted progress and clinical translation in this promising field. The overall goal of this proposed research is to generate, characterize, and apply photothermal nanocomposites for effective tissue repair. In this approach, we will generate nanocomposites in which, gold nanorods are incorporated within biocompatible biomacromolecules including, elastin-like polypeptides (ELPs), collagen, fibrin and their blends. The photothermal response of these nanocomposites will be investigated using both, pulsed and continuous wavelength lasers at different power intensities. In addition, the mechanical properties and efficacy of laser-triggered drug (MMP inhibitor) delivery from these nanocomposites will be determined (Specific Aim 1). Nanocomposites with effective photothermal properties will be investigated for their ability to repair ruptured porcine intestinal tissue ex vivo; an incision model of tissue rupture will be investigated. Both pulsed and continuous lasers, at different power intensities, will be investigated in order to facilitate nanocomposite-mediated localized photothermal welding of the ruptured tissue. Tensile strength, leak pressure and burst pressure will be investigated in order to determine the mechanical integrity of the nanocomposite-repaired tissue. The efficacy of photothermal nanocomposites for preventing bacterial leakage from bacteria-rich intestinal lumen will also be investigated. Nanocomposite composition and operating conditions that result in the most effective recovery of tissue properties compared to intact tissue will be identified (Specific Aim 2). The most effective nanocomposite type and operating conditions will be further evaluated for maintaining tissue integrity and facilitating repair in a mouse model of colon leakage. Mechanical properties, including burst pressures, biochemical and immune responses, effect of MMP inhibitor delivery, and photothermal effects will be determined following in vivo welding. Longer-term survival studies will also be carried out (Specific Aim 3). It is anticipated that the current research will lead to transformative developments in both, fundamental studies as well as application of biocompatible photothermal nanocomposites for tissue repair. Findings from this research have very high potential for direct translation to several clinical applications that can benefit from the several advantages of photothermal tissue repair.